Gene Therapy for Fracture Repair
Abstract
In the first year of this study, we have developed gene therapy approaches for fracture repair by: 1) identifying regulatory sequences providing maximum transgene expression by two gene therapy vectors in the bone cells that mediate fracture repair; 2) developing vector delivery techniques for optimal therapeutic gene expression in the healing fracture; and 3) identifying therapeutic gene candidates to augment and accelerate fracture repair. Maximum transgene expression in primary and transformed bone cells was obtained using the non-specific murine leukemia (MLV) -based long terminal repeat and the lentiviral cytomegalovirus promoters, and the gene-specific elongation factor 1a promoter with the lentiviral-based vector. Using the MLV-based vector, surgical techniques have been developed to deliver gene therapy to the fracture site and optimize transgene expression for optimal therapeutic effect. These techniques have benefited healing by augmenting BMP-4 mediated bone formation in the fracture gap. The healing fracture tissues of four individual subjects have been examined for gene expression by microarray analysis at both 3 days and 11 days healing to identify therapeutic gene candidates. Several hundred genes and expressed sequence tags displayed statistically significant changes in expression at each time. Several candidates are currently undergoing confirmation of expression and further functional characterization.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2003
- Accession Number
- ADA431895
Entities
People
- David J. Baylink